Iodine and iodine complex preparations are widely employed as disinfectants in human and veterinary medicine. Iodine has a powerful bactericidal and fungicidal action and is also active against viruses. It is used as topical antiseptic agents for treatment of small wounds, abrasions and other skin lesions such as herpes simplex. Iodine containing compositions are used for protective treatment of a skin area to be dissected.
Iodine preparations are used in veterinary medicine as post-milking disinfecting treatment of the udders. Iodine is also effectively used for disinfection of drinking water and swimming pool water (Martindale, The extra pharmacopoeia, [28TH] edition, Eds.: Reynolds, J. E. F. and Prasad, A. B., The Pharmaceutical Press, London, 1982, pp. 862-864).
Topical iodine preparations possess counter-irritating activity in rheumatism, tenosynovitis and in inflammatory diseases of the peripheral nervous system and muscles. Additional pronounced counter-irritating activity of iodine was demonstrated against skin irritation caused by chemical and thermal stimuli. Iodine is also effective against other skin irritants such as mechlorethamine, divinylsulfone, iodoacetic acid and cantharidine (Wormser et al. Arch. Toxicol. (1997) 71, 165-170).
Molecular iodine (I2) is practically water insoluble unless iodide (sodium or potassium salts) is present in the solution to form the water-soluble ion (I3−). Iodine can be dissolved in ethanol but precipitates in the presence of water. Thus, iodine tincture (which contains ethyl alcohol and water) must also contain iodide to form I3− for proper dissolution.
Iodine formulations using other solvents or carriers are known. In some cases, these formulations are shown to have greater iodine solubility or improved iodine release. In some cases, the iodine formulations are demonstrated to be more potent as antiseptics than currently available commercial iodine preparations.
Post-exposure treatment with topical povidone (polyvinylpyrolidone)-iodine preparation has been shown to provide significant protection against mustard gas (sulfur mustard, SM)-induced skin lesions (Wormser et al. Arch. Toxicol. (1997) 71, 165-170). Studies also have shown the counter-irritating activity of povidone-iodine against thermal stimuli in humans (Wormser, Burns (1998) 24, 383). The experience with patients after accidental heat burns (mostly of grade I; caused by hot water or oil or by hot steam) has shown that topical application of povidone-iodine ointment immediately after the stimulus reduced the degree of skin lesions. The shorter the interval between stimulus and treatment the better the protection achieved.
U.S. Pat. No. 5,071,648 discloses a composition containing acetalized polyvinyl alcohol complexed with iodine, which releases free iodine in the presence of water.
WO 01/70242 discloses a composition including molecular iodine and tetraglycol (TG) that facilitates the dissolution of iodine, enhances its antiseptic effect, and remains stable in the presence of water, in contrast to other iodine solvents, such as ethanol, in which iodine precipitates after water addition. Povidone-iodine complex (PVP-I) may also be dissolved in TG or a TG water system. A pharmaceutically acceptable vehicle according to WO 01/70242 includes an oil/water or a water/oil emulsion, a solution, a suspension, a gel, an ointment, a patch, or an aerosol, preferably solutions, gels and washable ointments.
Despite many years of usage in topical therapy, iodine compositions are still restricted to the conventional list of dosage forms, consisting of water/oil emulsions, solutions, suspensions, gels, ointments, patch, or aerosols. All these preparations comprise liquid or semi-liquid substances, having continuous texture and consistency and possessing specific gravity of 0.7-1.1. Such preparations are disadvantageous, when intended to treat relatively large areas. They are even more disadvantageous when the area to be treated is sensitive, such as area with burns or open wounds, where rubbing a liquid or semi-solid formulation is difficult and painful.
Certain foamable formulations are known in the art.
U.S. Pat. No. 5,716,611 discloses a topical formulation comprising an anti-microbially effective amount of povidone-iodine and from 2% to about 30% of a water-soluble emollient comprising from about 1 to about 99% ethoxylated higher aliphatic alcohol and from about 1 to about 99% ethoxylated cholesterol derivative. The composition includes thickening agents and surfactants that provide foaming upon rubbing on the applied surface.
U.S. Pat. No. 6,258,374 provides a pharmaceutical composition for rectal or vaginal application containing at least two parts wherein the composition comprises (i) two or more physiologically acceptable substances each in separate parts of the composition which are such that on admixture they react to produce a physiologically acceptable gas; (ii) in at least one part of the composition a polymer stabilizer which is adapted to facilitate the formation of a water-soluble collapsible foam structure; and (iii) in at least one part of the composition a pharmaceutically active substance. One of the optional active substances is iodine.
International patent application WO 96/19921 discloses a composition having biocidal activity comprising an active agent selected from iodine or a compound or complex thereof and a polymeric solubilizing agent. The composition may be a foam.
U.S. Pat. No. 6,187,290 teaches physiologically acceptable foam including a foamable carrier separately packaged from an active ingredient. The active ingredient may be, among others, povidone-iodine. Surfactants, humectants and plasticizers may be optionally included.
U.S. Pat. No. 5,951,993 discloses a composition including a lower alcohol and water in a weight ratio of about 35:65 to 100:0, and a thickener system. The thickener system includes at least two emulsifiers, each emulsifier containing at least one hydrophobic group and at least one hydrophilic group. The composition optionally contains iodine or a complexed form of iodine. The composition is useful as a presurgical scrub replacement, a lotion or other hand preparation.
U.S. Pat. No. 5,672,634 describes a rigid, cellular PVP-I foam product, useful as an iodophor, containing about 0.1-2% cross linker and about 16-18% total inorganic iodine.
U.S. Pat. No. 5,545,401 teaches a foaming gel consisting essentially of water, povidone and iodine. In one embodiment water is added to the gel in a closed container pressurized at between 1 and 3 atmospheres with pentane so that when the mixture is returned to atmospheric pressure it spontaneously forms a foam.
U.S. Pat. No. 5,254,334 describes an anhydrous cream composition comprising (a) glycerin in an amount from about 40% to about 60% by weight based on the weight of the total composition; (b) sodium cocoyl isethionate in an amount from about 10 to about 19% by weight based on the weight of the total composition; (c) emollients in an amount from about 10 to about 40% by weight based on the weight of the total composition; and (d) sodium lauryl sulfate in an amount from about 1 to about 5% by weight based on the weight of the total composition. The composition may further comprise a foam booster or active ingredients such as PVP-iodine.
U.S. Pat. No. 4,271,149 discloses a germicidal iodine composition containing an aqueous solution of elemental iodine and at least one organic substance which slowly reacts with iodine selected from the group consisting of iodine complexing polymers, surface active agents, alcohols, polyols and water soluble solvents. The iodine composition is stable for extended storage by providing balanced sources of iodide ion in the range of about 0.025% to 0.5% and iodate ion in the range of about 0.005% to 0.2% while maintaining a pH within the range of pH 5-7. Foam stabilizers are optional components of the composition.
New topical dosage forms are desired to deliver iodine and to treat skin conditions that respond to iodine topical application. A simple-to-use breakable foam, having low specific gravity and being easily spreadable on large skin areas, is particularly desirable.